title: Ergosterol peroxide from Cordyceps cicadae ameliorates TGF-β1-induced activation of kidney fibroblasts.
abstract: Chronic kidney disease is a growing public health problem with an urgent need for new pharmacological agents. Ergosterol peroxide (EP) is the major sterol produced by Cordyceps cicadae Shing (C. cicadae), a widely used traditional Chinese medicine. C. cicadae has been used to treat many kinds of diseases and has a potential benefit on renoprotection. This study aimed to investigate the anti-fibrotic effects of EP as well as the underlying mechanisms. A normal rat kidney fibroblast cell line (NRK-49F) was stimulated to undergo fibroblast activation by transforming growth factor-β1 (TGF-β1) and EP treatment was applied to explore its potential anti-fibrotic effects. Cell proliferation was investigated using MTT analysis. Fibrosis-associated protein expression was analyzed using immunohistochemistry and/or Western blotting. EP treatment attenuated TGF-β1-induced renal fibroblast proliferation, expression of cytoskeleton protein and CTGF, as well as ECM production. Additionally, EP blocked TGF-β1-stimulated phosphorylation of ERK1/2, p38 and JNK pathway. Moreover, the TGF-β1-induced expression of fibronectin was attenuated by either inhibition of MAPKs or by EP treatment. In conclusion, our findings demonstrate that EP is able to suppress TGF-β1-induced fibroblasts activation in NRK-49F. This new information provides a line of theoretical evidence supporting the use of C. cicadae in the intervention of kidney disease and suggests that EP has the potential to be developed as a therapeutic agent to prevent renal fibrosis.
authors.affiliation: Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zheng
authors.affiliation: Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: lhkidney@hotmail.com.
authors.forename: Yueyi
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Shuwei
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D032661:Cordyceps / Q000737:chemistry*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D004365:Drugs, Chinese Herbal; D005353:Fibronectins; D053773:Transforming Growth Factor beta1; D020928:Mitogen-Activated Protein Kinases; C036071:ergosterol-5,8-peroxide; D004875:Ergosterol
keywords: Chronic kidney disease; Cordyceps cicadae; Ergosterol peroxide; Fibroblast-to-myofibroblast transdifferentiaton; TGF-β1